Epigenetic down-regulation of integrin α7 increases migratory potential and confers poor prognosis in malignant pleural mesothelioma

2015 ◽  
Vol 237 (2) ◽  
pp. 203-214 ◽  
Author(s):  
Viktoria Laszlo ◽  
Mir Alireza Hoda ◽  
Tamas Garay ◽  
Christine Pirker ◽  
Bahil Ghanim ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Pleural Mesothelioma ◽  
Down Regulation

scholarly journals Aminopeptidase N/CD13 as a potential therapeutic target in malignant pleural mesothelioma

2018 ◽  
Vol 51 (5) ◽  
pp. 1701610 ◽  
Author(s):  
Takahiko Otsuki ◽  
Taku Nakashima ◽  
Hironobu Hamada ◽  
Yusuke Takayama ◽  
Shin Akita ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Tumour Growth ◽  
Tumour Progression ◽  
Molecular Target ◽  
Aminopeptidase N ◽  
Pleural Mesothelioma ◽  
Tumour Angiogenesis ◽  
Potential Therapeutic Target

Angiogenesis is a crucial factor in the progression of malignant pleural mesothelioma (MPM) and antiangiogenic strategies might be effective against MPM. Aminopeptidase N (APN)/CD13 promotes tumour angiogenesis and is associated with poor prognosis; however, its clinical significance in MPM remains unclear.In 37 consecutive patients with surgically resected MPM, we evaluated the association between immunohistochemical APN/CD13 expression in resected tumours and survival. Additionally, the antitumour and antiangiogenic effects of MT95-4, a fully humanised anti-APN/CD13 monoclonal antibody, were evaluated in mice orthotopically implanted with EHMES-10 (abundantly expressing APN/CD13) and MSTO-211H (scarcely expressing APN/CD13) MPM cells.High tumour APN/CD13 expression was associated with poor prognosis in MPM patients (p=0.04), and MT95-4 treatment reduced tumour growth and angiogenesis in mice harbouring EHMES-10 but not MSTO-211H cells. Furthermore, in mice harbouring EHMES-10 cells, MT95-4 combined with cisplatin more effectively suppressed tumour progression than cisplatin alone.Taken together, these results suggest that APN/CD13 is implicated in the aggressiveness of MPM. Here, MT95-4 treatment reduced tumour progression likely by inhibiting angiogenesis, suggesting APN/CD13 as a potential molecular target for MPM treatment. Additionally, combination treatment with MT95-4 and cisplatin could represent a promising approach to treating MPM exhibiting high APN/CD13 expression.

scholarly journals Treatment of malignant pleural mesothelioma: current status and future directions

2016 ◽  
Vol 73 (2) ◽  
Author(s):  
X. Dhalluin ◽  
A. Scherpereel
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
European Society ◽  
Poor Prognosis ◽  
Asbestos Exposure ◽  
Therapeutic Strategies ◽  
Current Status ◽  
Pleural Mesothelioma ◽  
European Respiratory Society ◽  
Future Directions ◽  
Cell Therapies

Previously considered to be rare, malignant pleural mesothelioma (MPM) is a highly aggressive tumour that has become a very important issue over recent years due to its poor prognosis and its increasing incidence mostly linked to previous asbestos exposure. An optimal treatment for MPM is not established yet; new therapies and predictive tools are still needed in the management of this cancer. Thus the aim of this review is to provide clinicians clear and up-to-dated data on the latest therapeutic strategies for MPM patients in 2010. The guidelines recently proposed by the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS) taskforce are summarized here. The authors also briefly reviewed the future directions in MPM treatment including targeted therapies, gene or cell therapies.

scholarly journals Patient-derived malignant pleural mesothelioma cell cultures: a tool to advance biomarker-driven treatments

Thorax ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 1004-1008 ◽  
Author(s):  
Nikolaos I Kanellakis ◽  
Rachelle Asciak ◽  
Megat Abd Hamid ◽  
Xuan Yao ◽  
Mark McCole ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Ex Vivo ◽  
Cytotoxic T Cells ◽  
Pleural Mesothelioma ◽  
Ex Vivo Model ◽  
High Throughput Drug Screening ◽  
Aggressive Cancer ◽  
Malignant Pleural Mesothelioma Cell

Malignant pleural mesothelioma (MPM) is an aggressive cancer, associated with poor prognosis. We assessed the feasibility of patient-derived cell cultures to serve as an ex vivo model of MPM. Patient-derived MPM cell cultures (n=16) exhibited stemness features and reflected intratumour and interpatient heterogeneity. A subset of the cells were subjected to high-throughput drug screening and coculture assays with cancer-specific cytotoxic T cells and showed diverse responses. Some of the biphasic MPM cells were capable of processing and presenting the neoantigen SSX-2 endogenously. In conclusion, patient-derived MPM cell cultures are a promising and faithful ex vivo model of MPM.

Circulating tumor cell (CTC) as a significant clinical marker in epithelioid-type malignant pleural mesothelioma (MPM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7080-7080
Author(s):  
Kazue Yoneda ◽  
Fumihiro Tanaka ◽  
Shunichi Fukuda ◽  
Hayato Orui ◽  
Masaki Hashimoto ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Tumor Cell ◽  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Circulating Tumor Cell ◽  
Independent Prognostic Factor ◽  
Pleural Mesothelioma ◽  
Roc Curve Analysis ◽  
Clinical Marker ◽  
Significant Difference

7080 Background: Circulating tumor cell (CTC) is a surrogate of distant metastasis, and our preliminary study suggested that CTC detected by an EpCAM-based immuno-magnetic separation system (“CellSearch”) was a useful clinical marker in the diagnosis of malignant pleural mesothelioma (MPM) (Tanaka F. et al ASCO 2008). Methods: Patients who presented at our institute to receive pleural biopsy with suspicion of MPM were prospectively enrolled. CTCs in 7.5mL of peripheral blood were quantitatively evaluated with the CellSearch system. Results: Among 136 eligible patients, 104 were finally diagnosed with MPM, and 32 were with non-malignant diseases (NM). CTC was positive (CTC≥1) in 32.7% (37/104) of MPM pts, and in 9.4% (3/32) of NM pts (p=0.011). CTC-count was significantly higher in MPM (range, 0-9) than in NM (range, 0-1; p=0.007). According to a ROC curve analysis, the CTC-test provided a significant diagnostic performance in discrimination between MPM and NM (AUC= 0.623; P=0.036). Among MPM pts, CTC-positivity and CTC-count were significantly increased with tumor progression (p=0.026 and p=0.008, respectively). For all MPM pts, there was no significant difference in overall survival between CTC-positive and negative pts. However, in a planned subset analysis, CTC was a significant factor to predict poor prognosis (median survival time, 8.0 months for CTC-positive pts, and 20.3 months for negative pts; p=0.012) in pts with epithelioid-type MPM in which CTC was exclusively positive; a multivariate analysis confirmed that CTC, along with PS, was an independent prognostic factor (HR=2.38; P=0.006). Conclusions: CTC was a significant diagnostic marker in discrimination between MPM and NM. CTC-positivity was a significant and independent prognostic factor to predict a poor prognosis of epithelioid MPM. [Table: see text]

scholarly journals Up-regulation of Mitotic Nuclear Division-related Genes and Down-regulation of TGF-β-related Genes Correlate with Survival in Malignant Pleural Mesothelioma

2021 ◽  
Author(s):  
Lili Su ◽  
Yonggang Wang ◽  
Daowei Li ◽  
Xingguang Wang ◽  
Bin Liang ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Nuclear Division ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Pleural Mesothelioma ◽  
Related Gene ◽  
Down Regulation

Abstract Malignant pleural mesothelioma (MPM) is a highly aggressive and lethal malignancy; however, its molecular origins remain largely unknown. The purpose of this study was to use transcriptomics to explore the molecular mechanisms of MPM tumorigenesis toward gaining a better understanding of disease development. The transcriptomes from MPM tissues and paired normal pleural tissues were compared to identify significantly differentially expressed genes. These genes were then subject to Gene Ontology analysis to explore pathways that are dysregulated in MPM, and The Cancer Genome Atlas (TCGA) gene expression profile data were analyzed to assess the correlation between the significantly dysregulated pathways and patient survival. Moreover, three independent transcriptomic datasets were used to validate the association between significantly dysregulated genes and the clinical features of MPM. We identified 136 up-regulated and 599 down-regulated genes in MPM tissues as compared to normal pleural tissues. Functional enrichment analysis showed that the up-regulated genes were mainly associated with mitotic nuclear division, whereas the down-regulated genes were mainly associated with transforming growth factor beta (TGF-β) signaling. The 14 most significantly up-regulated mitotic nuclear division-related genes were more likely to be highly expressed in pathological subtypes with higher malignancy, whereas the down-regulated TGF-β pathway-related gene PPARGC1A displayed the opposite trend. In the TCGA dataset, up-regulation of mitotic nuclear division-related genes was associated with a poor prognosis, whereas down-regulation of TGF-β pathway-related genes was associated with a positive prognosis. The down-regulated PPARGC1A were further validated by immunohistochemical analysis. In summary, the correlation between up-regulation of mitotic nuclear division-related genes and down-regulation of the TGF-β pathway-related gene PPARGC1A with overall survival indicates an important role for these genes in MPM development and progression.

scholarly journals Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

PLoS ONE ◽  
2015 ◽  
Vol 10 (9) ◽  
pp. e0139312 ◽  
Author(s):  
Svenja Thies ◽  
Martina Friess ◽  
Lukas Frischknecht ◽  
Dimitri Korol ◽  
Emanuela Felley-Bosco ◽  
...  
Keyword(s):  
Stem Cell ◽  
Malignant Pleural Mesothelioma ◽  
Stem Cell Factor ◽  
Poor Prognosis ◽  
Pleural Mesothelioma

scholarly journals Oncological Frontiers in the Treatment of Malignant Pleural Mesothelioma

2021 ◽  
Vol 10 (11) ◽  
pp. 2290
Author(s):  
Emanuele Vita ◽  
Alessio Stefani ◽  
Mariantonietta Di Di Salvatore ◽  
Marco Chiappetta ◽  
Filippo Lococo ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Genomic Sequencing ◽  
Pleural Mesothelioma ◽  
Targeted Drugs ◽  
Treatment Algorithms ◽  
Rare Malignancy ◽  
New Generation ◽  
The Way

Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.

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